阅读说明：本技术 多取代n-芳基吡咯类化合物及其制备方法 (Polysubstituted N-arylpyrrole compound and preparation method thereof ) 是由 黄文博 柯少勇 王开梅 方伟 万中义 于 2020-04-29 设计创作，主要内容包括：本发明提供了一种多取代N-芳基吡咯类化合物及其制备方法,其结构为：<Image he="329" wi="236" file="DDA0002473227810000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其制备方法由芳香胺、溴乙醛缩二乙醇、1,3-二羰基化合物为原料在有机溶剂及催化条件下合成。该化合物结构新颖,具有酯基、羧基等活性位点,有利于进一步进行结构优化,开发出具有重要抗菌、杀虫和抗病毒活性的吡咯类化合物。同时,本发明中的制备方法使用的原料廉价易得、操作简单、工业应用价值大。(The invention provides a polysubstituted N-aryl pyrrole compound and a preparation method thereof, and the polysubstituted N-aryl pyrrole compound has the following structure:)

1. A polysubstituted N-arylpyrrole compound has a structural formula as follows:

wherein:

R¹is one of pyridyl, substituted pyridyl, oxazolyl, isoxazolyl, naphthyl, thienyl, furyl, quinolyl, phenyl or substituted phenyl, and the substituent on the substituted phenyl and the substituted pyridyl is one, two or three of alkyl, alkoxy, halogen, carboxyl, acetyl, trifluoromethyl and cyano;

R²is one of methyl, ethyl, propyl, phenyl, substituted phenyl, trifluoromethyl, pyridyl, furyl and naphthyl;

R³is one of alkyl, alkoxy, trifluoromethoxy, trifluoromethyl, furyl, thienyl, pyridyl, naphthyl, acetyl and phenylAnd (4) seed preparation.

2. The polysubstituted N-arylpyrrole compound of claim 1, wherein: the R is¹Is one of pyridyl, substituted pyridyl, phenyl or substituted phenyl.

3. The polysubstituted N-arylpyrrole compound of claim 1, wherein: the R is²Is one of methyl, phenyl, trifluoromethyl and pyridyl.

4. The polysubstituted N-arylpyrrole compound of claim 1, wherein: the R is³Is one of alkyl or alkoxy.

5. A preparation method of polysubstituted N-arylpyrrole compounds as claimed in claim 1, which is prepared by the full reaction of aromatic amine, bromoacetaldehyde diethyl acetal and 1, 3-dicarbonyl compounds as raw materials in an organic solvent under the catalysis condition, and the preparation reaction formula is as follows:

wherein the catalyst is an acid catalyst, and the organic solvent is any one of dichloromethane, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, ethanol and toluene.

6. The method for preparing polysubstituted N-arylpyrroles according to claim 5, wherein: the acid catalyst is one of ferric trichloride, boron trifluoride diethyl etherate, aluminum chloride, acetic acid, cupric bromide and p-toluenesulfonic acid.

7. The method for preparing polysubstituted N-arylpyrroles according to claim 5, wherein: the molar ratio of the aromatic amine to the bromoacetaldehyde diethyl acetal is 1: 2-2: 1, and the molar ratio of the aromatic amine to the 1, 3-dicarbonyl compound is 1: 1-1: 2.

8. The method for preparing polysubstituted N-arylpyrroles according to claim 5, wherein: the reaction temperature during preparation is 0-100 ℃, and the reaction time is 4-10 hours.

9. The method for preparing polysubstituted N-arylpyrroles according to claim 5, wherein: the molar ratio of the aromatic amine to the used catalyst is 20: 1-5: 1.

10. The method for preparing polysubstituted N-arylpyrroles according to claim 5, wherein: and separating the polysubstituted N-arylpyrrole compound crude product obtained by the reaction through silica gel column chromatography to obtain the polysubstituted N-arylpyrrole compound, wherein the volume ratio of an eluent of the silica gel column chromatography is 20: 1-5: 1 of petroleum ether and ethyl acetate.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a polysubstituted N-arylpyrrole compound and a synthesis method thereof.

Background

Pyrrole alkaloids are a very important compound in pharmaceutical chemistry and natural product chemistry research, are used as an important nitrogenous five-membered heterocycle, have wide biological activity and pharmacological activity, are core skeleton structures of a plurality of natural products and drug molecules, play a very key role in the fields of antibiosis, disinsection, antivirus, anticancer and the like, and a plurality of representative drugs containing pyrrole units and natural product molecules are listed in the following formula.

Because the polysubstituted pyrrole compounds have unique biological activity and are widely applied to medicines and natural products, the synthesis and preparation of the polysubstituted pyrrole compounds are always the research hotspots in organic synthesis and pharmaceutical chemistry. Such as the classical human name reactions Knorr, Hantzsch and Paal-Knorr, and the multi-component tandem reactions developed in recent years (Jad, y.e.; Gudimella, s.k.; goven der, t.; de la Torre, b.g.; Albericio, f.acs comb. sci.2018,20,187.Est é vez, v.; Villacampa, m.; Men e ndez, j.c.chem.soc. rev.2010,39,4402), transition metal catalysis (Bunrit, a.; sawaddjoon, s.;S.；P.J.R., Samec, J.S.M.J.org.chem.2016,81,1450.) and C-H activation (L ade, D.M.; Pawar, A.B.org.chem.Front.2016,3,836.) however, these existing methods for synthesizing polysubstituted pyrroles often have the disadvantages of pre-functionalization of substrates, high temperature and high pressure, noble metal catalysis and the like, so that a synthetic method with cheap and easily available substrates, good reaction selectivity and low economic cost is urgently needed.

Disclosure of Invention

Aiming at the defects or the improved requirements of the existing method for synthesizing the polysubstituted pyrrole, the invention aims to provide a polysubstituted N-aryl pyrrole compound which is simple, efficient and low in cost and a preparation method thereof.

In order to achieve the purpose, the polysubstituted N-arylpyrrole compound has a structure shown as a general formula I:

wherein: r¹Is one of pyridyl, substituted pyridyl, oxazolyl, isoxazolyl, naphthyl, thienyl, furyl, quinolyl, phenyl or substituted phenyl, and the substituent on the substituted phenyl and the substituted pyridyl is one, two or three of alkyl, alkoxy, halogen, carboxyl, acetyl, trifluoromethyl and cyano;

R²is one of methyl, ethyl, propyl, phenyl, substituted phenyl, trifluoromethyl, pyridyl, furyl and naphthyl;

R³is one of alkyl, alkoxy, trifluoromethoxy, trifluoromethyl, furyl, thienyl, pyridyl, naphthyl, acetyl and phenyl.

Preferably, said R is¹Is one of pyridyl, substituted pyridyl, phenyl or substituted phenyl.

Further preferably, R²Is one of methyl, phenyl, trifluoromethyl and pyridyl.

Even further preferably, R³Preferably one of an alkyl or alkoxy group.

The invention also provides a preparation method of the polysubstituted N-aryl pyrrole compound, which is synthesized by taking aromatic amine, bromoacetaldehyde diethyl acetal and a 1, 3-dicarbonyl compound as raw materials in an organic solvent under the catalysis condition, and the synthetic route is as follows:

wherein the catalyst is an acid catalyst, and the organic solvent is any one of dichloromethane, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, ethanol and toluene. The acid catalyst is one of ferric trichloride, boron trifluoride diethyl etherate, aluminum chloride, acetic acid, cupric bromide and p-toluenesulfonic acid.

The molar ratio of the aromatic amine to the bromoacetaldehyde diethyl acetal is 1: 2-2: 1, and the molar ratio of the aromatic amine to the 1, 3-dicarbonyl compound is 1: 1-1: 2.

The reaction temperature during preparation is 0-100 ℃, the preferable temperature is 60-80 ℃, and the reaction time is 4-10 hours.

The molar ratio of the aromatic amine to the used catalyst is 20: 1-5: 1.

And separating the polysubstituted N-arylpyrrole compound crude product obtained by the reaction through silica gel column chromatography to obtain the polysubstituted N-arylpyrrole compound, wherein the volume ratio of an eluent of the silica gel column chromatography is 20: 1-5: 1 of petroleum ether and ethyl acetate.

The polysubstituted N-aryl pyrrole provided by the invention has a novel structure, has active sites such as ester group, carboxyl and the like, is favorable for further structural optimization, and develops a pyrrole compound with important antibacterial, insecticidal and antiviral activities. Meanwhile, the preparation method has the advantages of cheap and easily-obtained raw materials, simple operation and high industrial application value, and in addition, the reaction conditions are optimized (especially aiming at the amount of reactants, the reaction temperature, the reaction time and the like), so that the reaction selectivity is good, the yield is high, and the method has obvious advantages compared with the existing method for synthesizing the polysubstituted pyrrole.

Detailed Description

The polysubstituted N-arylpyrrole compounds and the preparation method thereof of the present invention will be described in further detail with reference to the following specific examples.